Rhythmic motor systems, like all neural circuits, depend heavily on many different neuromodulatory substances such as neuropeptides and amines for their function. The crustacean stomatogastric nervous system is an ideal preparation for the study of the organization of cotransmission systems and modulator function because it produces easily measurable motor patterns, and can be readily perturbed. The proposed experiments will: 1) determine the target neurons for 13 different neuromodulatory agents within the stomatogastric ganglion, 2) describe the effects of neuromodulators and electrical coupling on the frequency and waveform of a three neuron pacemaker network, 3) explore the roles of cotransmitters with apparently opposing actions on a sensory neuron's activation of plateau properties, 4) explore the consequences of perturbing the modulatory environment during embryonic development, and 5) study the long-term regulation of neuromodulator responses subsequent to removal of descending modulatory pathways to the stomatogastric ganglion. Together these data will add to our understanding of how neurons and networks that are modulated by many different substances control their responses to many of their input modulators. This work has relevance to mental illnesses and diseases that can be viewed as failures of neuromodulatory balance, such as depression and schizophrenia. More specifically, these data will provide basic understandings of some of the processes that may occur in spinal cord central pattern generating networks deprived of their modulatory input as a consequence of spinal cord lesions.